A current look at the in vitro activity of oritavancin and vancomycin against isolates of S.aureus from both Europe and the US

Abstract number: P1637

Draghi D., Pillar C., Sahm D., Moeck G., Arhin F.

Background: Reports have emerged regarding an upward shift in vancomycin (VAN) MICs against S. aureus (SA) and the impact of elevated VAN MICs on clinical outcome. Oritavancin (ORI), a lipoglycopeptide, is currently under development for the treatment of Gram-positive infections. It is important to understand ORI activity as it relates to SA isolates with elevated VAN MICs (should these isolates become more prevalent). This study evaluates the trend in VAN MICs observed among recent surveillance (SURV) isolates (2005–2008) and the activity of ORI activity against SURV isolates with defined VAN MICs (0.25/0.5/1/2 mg/L).

Methods: SA clinical isolates collected in 2005–2008 (n = 8,186) from geographically diverse SURV studies in the US and Europe (EU) were centrally tested by broth microdilution (CLSI; M7-A7) against ORI and VAN in accordance with CLSI M100-S18.

Results: With the exception of an increasing trend in the amount of isolates with VAN MICs of 1 mg/L from 2005–2007 in the US, no notable MIC creep for VAN was apparent among SURV isolates, with a consistent mode, MIC50 and MIC90 of 1 mg/L. Interestingly, SURV isolates from EU and the US in 2008 had more isolates with VAN MICs of 0.5 mg/L than in prior years. Similarly, a lower overall ORI MIC50/MIC90 (mg/L) in 2007 and 2008 was observed (0.03/0.06 US; 0.03/0.12 EU) relative to 2005 and 2006 (0.06/0.12 US; 0.06/0.25 EU). Against SA with VAN MICs of 0.5 and 1 mg/L, ORI maintained potent activity with MIC50 s from 0.03–0.06 mg/L and MIC90 s 0.06–0.25 mg/L among evaluated SURV isolates from 2005–2008. However, ORI MIC50 s and MIC90 s against SA with VAN MICs of 2 mg/L (MIC50 s of 0.12–0.25 mg/L; MIC90 s of 0.25 mg/L) were slightly higher relative to isolates with VAN MICs 1 mg/L over this period.

Conclusions: Apart from a slight upward shift in VAN MICs apparent with US isolates from 2005–2007, little evidence for VAN MIC creep was evident with isolates from large scale SURV studies. In fact, VAN MICs in 2008 tended to be slightly lower than those from 2005–2007. Regardless, ORI MIC50 s and MIC90 s were consistent and lower than VAN against SA with defined VAN MICs of 0.5, 1, or 2 mg/L, though ORI MICs were slightly elevated against the small subpopulation of isolates with VAN MICs of 2 mg/L. Future SURV is warranted to monitor for shift in VAN MICs and its effect, if any, on the activity of ORI.